Shibafuji Yusuke, Nagao Nobuyoshi, Yohda Masafumi
R & D Center, AGC Biologics, Washington, USA.
Institute of Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan.
Biotechnol J. 2023 Jul;18(7):e2200638. doi: 10.1002/biot.202200638. Epub 2023 May 15.
Multi-omics analyses was performed to compare the conditions of adding Tyr and Cystine in CHO cells. The addition of cystine resulted in decreased viability and productivity owing to endoplasmic reticulum (ER) stress and the promotion of ER-associated degradation (ERAD) and apoptosis. In contrast, addition of Tyr suppressed ER stress and apoptosis. This effect could be due to the increase in ubiquinone (Coenzyme Q10) biosynthesized from Tyr. To inhibit apoptosis caused by cystine addition, Tyr was added simultaneously with cystine, which improved growth, viability, and mAb productivity owing to the activation of GSH metabolism, suppression of ER stress and oxidative stress, reduction of ERAD, and activation of the tricarboxylic acid cycle.
进行多组学分析以比较在CHO细胞中添加酪氨酸(Tyr)和胱氨酸的情况。添加胱氨酸会由于内质网(ER)应激以及内质网相关降解(ERAD)和细胞凋亡的促进而导致活力和生产力下降。相比之下,添加酪氨酸可抑制内质网应激和细胞凋亡。这种效应可能归因于由酪氨酸生物合成的泛醌(辅酶Q10)增加。为了抑制因添加胱氨酸引起的细胞凋亡,将酪氨酸与胱氨酸同时添加,这由于谷胱甘肽(GSH)代谢的激活、内质网应激和氧化应激的抑制、ERAD的减少以及三羧酸循环的激活而改善了生长、活力和单克隆抗体(mAb)的生产力。